NCT06835049

Feasibility of Total Neoadjuvant Treatment With HYPErthermia in Patients With High-risk Extremity and Trunk Soft Tissue Sarcoma (TNT-HYPE)

Feasibility of Total Neoadjuvant Treatment With HYPErthermia in Patients With High-risk Extremity and Trunk Soft Tissue Sarcoma (TNT-HYPE). A Multicenter, Single Arm, Open Label, Phase II Trial

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Swiss Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Soft tissue sarcomas (STSs) are rare cancers with a 5-year survival rate of 60%, and there is no standard treatment for high-risk extremity and trunk STSs (eSTS). A phase III trial suggests that adding moderate regional hyperthermia (HT) to anthracycline-based chemotherapy, followed by surgery and radiotherapy (RT), can improve 10-year overall survival by 10%. This trial aims to optimize treatment by combining the most effective regimens from chemotherapy, HT, RT, and surgery, and will evaluate the feasibility of this new total neoadjuvant treatment (TNT) approach.

Detailed description

Soft tissue sarcomas (STSs) are rare cancers with a 5-year survival rate of only 60%. There is no international standard treatment for high-risk extremity and trunk STSs (eSTS). Current evidence from a phase III trial suggests that adding moderate regional hyperthermia (HT) to anthracycline-based chemotherapy followed by surgery and radiotherapy (RT) can improve survival rates, showing a 10% improvement in 10-year overall survival. The aim of this trial is to optimize the treatment for this high-risk group. To achieve this, the assumed most effective treatment regimens from each treatment modality (chemotherapy, HT, RT, and surgery) were identified and combined into an optimized treatment protocol. Neoadjuvant chemotherapy in this population is not yet broadly accepted as standard of care. Furthermore, this new total neoadjuvant treatment (TNT) approach has not yet been investigated prospectively and in addition, the patients have to get their HT treatment potentially in a hospital distant from their domicile. Therefore, we will evaluate in this trial the feasibility of this new treatment schedule as primary endpoint. Trial treatment consists of 3 neoadjuvant cycles of doxorubicin with either ifosfamide or dacarbazine (the latter only in case of leiomyosarcoma) combined with HT, followed by RT and surgery. Each chemotherapy cycle will last 3 weeks. Trial treatment will last approximately 20 weeks. After surgery, a follow-up period of 36 months per patient is foreseen.

Conditions

• Sarcoma,Soft Tissue

Interventions

Type	Name	Description
DRUG	Doxorubicin	Trial treatment consists of 3 neoadjuvant cycles of doxorubicin with either ifosfamide or dacarbazine (the latter only in case of leiomyosarcoma). Doxorubicin will be given at a dose of 75 mg/m2 Body surface area (BSA) on day 1 of each cycle as a intravenous infusion over 15 minutes.
DRUG	Ifosfamide	Trial treatment consists of 3 neoadjuvant cycles of doxorubicin with either ifosfamide or dacarbazine (the latter only in case of leiomyosarcoma). Ifosfamide will be given at a dose of 3 g/m2 BSA on days 1 to 3 of each cycle, for a total dose per cycle of 9 g/m2 BSA, as an intravenous infusion of 3 g/m2 daily over 4 hours.
DRUG	Dacarbazine	Trial treatment consists of 3 neoadjuvant cycles of doxorubicin with either ifosfamide or dacarbazine (the latter only in case of leiomyosarcoma). Dacarbazine will be given at a daily dose of 300 mg/m2 BSA on days 1 to 3 of each cycle, for a total dose per cycle of 900 mg/m2 BSA, as an intravenous infusion over 30 minutes.
OTHER	Hyperthermia	Hyperthermia (HT) sessions are scheduled on days 1 and 3 of each chemotherapy cycle. The duration of the preheating phase is always 30 minutes. Together with the treatment phase of 60 minutes, the duration of a HT session is uniformly 90 minutes (Total treatment time). On days 2, chemotherapy will be applied without HT.
RADIATION	Radiotherapy	Radiotherapy (RT) treatment should start ideally 19 days after last chemotherapy dose received (range -4 / +7), preferably on a Monday to omit that the last RT fractions will be applied directly after the weekend. Start of RT can be postponed up to 14 days due to medical reasons without violating treatment protocol. Patients will preferably receive normofractionated RT to a total dose of 50 Gy in 25 fractions of 2 Gy over 5 weeks23. Alternatively, patients can receive a moderate hypofractionated RT to either a total dose of 42.75 Gy in 15 fractions of 2.85 Gy over 3 weeks or a total dose of 42 Gy in 14 fractions of 3 Gy over 2 weeks and four days41. The respective total treatment time changes respectively. The RT treatment should be delivered once daily except on weekends.
PROCEDURE	Surgery	Standard of care surgical resection must be done by an experienced sarcoma surgeon. All lesions of the trunk and extremities will be resected after total neoadjuvant treatment with chemotherapy, HT and RT. Surgery will take place preferentially 6 weeks (+/- 2 weeks) after end of radiation.

Timeline

• Start date: 2025-10-27
• Primary completion: 2028-03-31
• Completion: 2031-03-31
• First posted: 2025-02-19
• Last updated: 2025-12-30

Locations

8 sites across 1 country: Switzerland